Abstracts

Rationale: The ketogenic diet(KD) is an effective dietary treatment of intractable epilepsy (IE). It is a high fat, low carbohydrate and protein diet. Growth failure with the KD has been reported and several studies have shown deceleration in height Z-scores. Insulin-like growth factor 1 (IGF-Ι) is the principal mediator of prepubertal growth in humans, but has not previously been investigated in children treated with the KD. The purpose of this study was to evaluate the response of IGF-Ι over 15 months in children with IE treated with the KD, and to elucidate the relationship of IGF-Ι and growth status during KD initiation. Methods: Children with IE were eligible. The KD was initiated using either a gradual (GRAD-KD) or a fasting protocol (FAST-KD). Measurements were obtained at baseline, 3, 6, 9, 12, and 15 months of KD therapy. Serum IGF-Ι was analyzed using standard Human IGF-1 Immmunoassay by Quantikine. IGF-Ι is presented as a Z-score adjusted for age and gender. Height (HAZ), weight (WAZ), and BMI (BMIZ) were measured and Z-scores calculated. Statistical analyses included descriptive, multiple regression and longitudinal mixed effects (LME) analyses. Results: 22 children (82% males, age 5.5±2.5 yr, 41% with GRAD-KD initiation)had IGF-Ι status assessed. Before the initiation of the KD, IGF-1Z was normal (0.2±1.7), and growth status was suboptimal (HAZ -0.4±1.1; WAZ -0.6±1.6; BMIZ -0.4±1.9). After three months of KD therapy, IGF-ΙZ declined precipitously to -2.3±1.5 and remained low through 15 months (-3.1±0.9). All measures of growth status declined by approximately -0.1 Z score after 3 months. By multiple regression, significant positive predictors of IGF-ΙZ at 3 months were IGF-ΙZ at baseline, age and GRAD-KD. LME models showed that IGF-ΙZ was significantly positively associated (p=0.008) with HAZ which declined significantly (-0.51, p=0.001) over 15 months of KD therapy. Boys tended to have higher IGF-ΙZ than girls (p=0.058). WAZ did not significantly change from 3 to 15 months. Conclusions: Prior to treatment with the KD, children with IE had relatively normal IGF-Ι status despite having suboptimal growth status. IGF-ΙZ declined sharply in the first 3 months of KD therapy. Sustained low levels of IGF-ΙZ were associated with progressive decline in HAZ over 15 months. GRAD-KD initiation was associated with less severe decline in IGF-ΙZ levels in these children.